Engineered donor T-cells may eradicate progressive disease after stem cell transplantation in patients with B-cell malignancies

Findings from an early clinical study suggest that infusing anti-CD19 donor chimeric antigen receptor (CAR) T-cells is a promising method for the treatment of B-cell malignancies that emerge after stem cell transplantation. In fact, a single infusion of CAR T-cells, obtained from each recipient’s stem cell donor, without additional chemotherapy or other therapies, led to a remission in 8 out of 20 patients with resurgence of a B-cell malignancy after a stem cell transplantation. Interestingly, this procedure did not lead to a graft-versus-host reaction in any of the patients.

Relapse represents the leading cause of death in patients undergoing an allogeneic stem cell transplantation (alloHSCT). After an alloHSCT, B-cell malignancies are often treated with infusions of unmanipulated donor lymphocytes (DLIs) from the transplant donor. However, DLIs are frequently not effective at eradicating malignancy, and often cause graft-versus-host disease (GVHD), which is a potentially lethal allogeneic immune response against normal recipient tissues.

In the presented clinical trial, the hypothesis was tested whether allogeneic T-cells, that were genetically engineered to express a CAR targeting the B-cell antigen CD19, would eradicate progressive disease after a alloHSCT in patients with B-cell malignancies. Patients with B-cell malignancies after alloHSCT received a single infusion of CAR T-cells, without administering chemotherapy or other therapies. The T-cells were obtained from each recipient’s alloHSCT donor.

In total, 20 patients were enrolled in the study. A remission was achieved in 8 patients, including 6 complete and 2 partial remissions. The response rate was highest in the 5 patients with acute lymphocytic leukemia, where 4 patients obtained an MRD-negative complete remission. Two of these patients later relapsed, but 1 patient is in ongoing complete remission at 18 months. The fourth patient went for a second alloHSCT while in complete remission. Of the 5 patients with chronic lymphocytic leukemia, 1 patient obtained a complete remission and 1 patient had a partial response. In 2 patients stable disease was reported. Both the complete and the partial remission are still ongoing at 36 and 18 months respectively. Among the 5 patients with a recurrent mantle cell lymphoma, 1 complete and 1 partial remission were seen and 3 patients had stable disease. Interestingly, the complete remission in this mantle cell lymphoma patient is still ongoing at 31 months. Finally, 3 out of 5 patients with a diffuse large B-cell lymphoma had stable disease after the CAR T-cell therapy (1 patient still ongoing), 1 patient had a complete response and 1 patient had disease progression.

Not a single patient developed new-onset acute GVHD after CAR T-cells were infused. Toxicities included fever, tachycardia, and hypotension. The median peak blood CAR T-cell levels were higher in patients who obtained a remission (39 CAR+ cells/mL) than in patients who did not obtain a remission (2 CAR+ cells/mL, p= 0.001). The presence of endogenous normal or malignant blood B-lymphocytes before CAR T-cell infusion was shown to be associated with a higher post-infusion median blood CAR T-cell level (p= 0.04). Compared to patients who did not obtain a remission, patients obtaining remissions had a higher CD8:CD4 ratio of blood CAR+ T cells at the time of peak CAR T-cell levels (p= 0.007). The mean percentage of CAR+CD8+ T cells expressing the programmed cell death-1 (PD-1) protein increased from 12% at the time of infusion to 82% at the time of peak blood CAR T-cell levels (p < 0.0001). Similarly, the mean percentage of CAR+CD4+ T cells expressing PD-1 increased from 32% at the time of infusion to 91% at the time of peak blood CAR T-cell levels (p < 0.0001).

In summary, the findings support the hypothesis that infusing anti-CD19 donor CAR T cells is a promising method for treating B-cell malignancies emerging after stem cell transplant.


Brudno J, Somerville R, Shi V, et al. Allogeneic T-Cells Expressing an Anti-CD19 Chimeric Antigen Receptor Cause Remissions of B-Cell Malignancies after Allogeneic Hematopoietic Stem Cell Transplantation without Causing Graft-Versus-Host Disease. Presented at ASH 2015; Abstract #99.

Speaker James Kochenderfer


James N. Kochenderfer, MD
physician-scientist, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA


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